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Leprosy (Hansen's Disease)

Leprosy (Hansen's Disease) is a chronic infectious disease that primarily affects the peripheral nerves, skin, upper respiratory tract, eyes, and nasal mucosa (lining of the nose). The disease is caused by a bacillus (rod-shaped) bacterium known as Mycobacterium leprae.

Researchers are exploring more avenues than ever before in the search for solutions to leprosy, now that the genome of M. leprae has been sequenced. NIAID's goals are to discover reservoirs of infection, routes of transmission, and incubation periods so the disease can be stopped before patients even have symptoms. New tests for early detection of leprosy before nerve damage occurs are now being developed.

What's New

Understanding Leprosy

Leprosy (Hansen’s Disease), is a chronic infectious disease that primarily affects the peripheral nerves, skin, upper respiratory tract, eyes, and nasal mucosa. The disease is caused by a bacillus (rod-shaped) bacterium known as Mycobacterium leprae.

The Bacterium: Mycobacterium leprae

M. leprae, discovered by G.A. Hansen in Norway in 1873, is a slow-growing, intracellular pathogen that cannot live outside its host. Because it can only be grown in animals, not in a laboratory, it is more difficult to study than other bacteria. Armadillos and immunocompromised mice are the two primary sources for growing the bacteria for research purposes.

Another factor complicating studies of leprosy is that M. leprae multiplies slowly, and symptoms can take as long as 20 years to appear. Armadillos are the only animals other than humans that have been found to become naturally infected with M. leprae.

The Disease

Researchers are still unclear about the mode of transmission of leprosy. Though widely assumed to be spread via the respiratory system through nasal droplets, broken skin is also a possibility. Because M. leprae survive best at low temperatures, it primarily affects the superficial sites of the skin and peripheral nerves.

Susceptibility to infection with M. leprae appears to be genetic, and the form of disease that a person develops depends on the immunity of infected people. Some people in a family may have the infection, but other close family members will not develop it, depending on their personal ability to fight off the bacteria.

Leprosy usually affects the skin, peripheral nerves, and upper airways but has a wide range of clinical manifestations. Clinical forms of leprosy represent a spectrum reflecting the cellular immune response to M. leprae. Patients with good T-cell immunity (Th1 type) towards M. leprae exhibit tuberculoid (TT) leprosy which is also known as pauci-bacillary leprosy, a milder form of the disease, characterized by skin discoloration. Those with poor T-cell immunity towards M. leprae typically exhibit lepromatous (LL) leprosy or multi-bacillary leprosy, which is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in congestion and nose bleeds. In between these forms of leprosy are the borderline tuberculoid (BT), borderline-borderline (BB) and borderline lepromatous (BL) forms.

LL leprosy is also characterized by large numbers of organisms in the skin, many skin lesions with slight hypopigmentation, and less sensory loss in the lesions. While people with LL have high titer antibodies to M. leprae, they also have an impaired cellular immune response to the bacillus. Changes in immunity of the host as well as treatment can result in worsening of the clinical course of the disease.

All forms of leprosy may cause some degree of peripheral neurological damage (nerve damage in the arms and legs) that causes sensory loss in the skin as well as muscle weakness. People with long-term leprosy may lose the use of their hands or feet due to repeated traumatic injury resulting from lack of sensation. If left untreated, it can cause progressive and permanent damage to the skin, nerves, eyes, and limbs.

Diagnosis and Treatment

In the United States, most physicians do not have experience identifying leprosy because it is extremely rare (about 100 to 200 new cases per year, mostly occurring in the Gulf Coast, Hawaii, Massachusetts, and New York or among people who have lived in areas of the world where the disease is more widespread). It is important that people who have unusual rashes that do not respond to treatment seek out skilled dermatologists who can make an accurate diagnosis.

Diagnosis of leprosy is typically based on clinical symptoms, especially localized skin lesions that show sensory loss (loss of sensation to stimuli such as touch and heat). Thickened, enlarged peripheral nerves are also a hallmark of the disease. To reach a conclusive diagnosis, healthcare providers should test skin samples.

With early diagnosis, leprosy can be treated. People who are being treated for leprosy are not contagious, and they can lead a normal lifestyle.

In 1981, the World Health Organization recommended multidrug therapy with dapsone, rifampicin, and clofazimine. In the United States, the regimen provides all drugs on a daily basis with multibacillary cases treated for 2 years and paucibacillary cases treated for 1 year. Additional information on diagnostic support, treatment regimens and the use of alternate drugs is available from the National Hansen’s Disease Program.

History of the Disease

Leprosy was well recognized in the oldest civilizations of China, Egypt, and India. The first known written reference to leprosy appeared in an Egyptian papyrus document written around 1550 BC.

Throughout history, leprosy has been feared and misunderstood, and has resulted in significant stigma and isolation of those who are afflicted. It was thought to be a hereditary disease, a curse, or punishment from the gods. During the Middle Ages, those with leprosy were forced to wear special clothing and ring bells to warn others as they walked by.

A cumulative total of the number of people who, over the millennia, have suffered its chronic course of incurable disfigurement, physical disabilities, or psychological trauma can never be estimated. There are many countries in Asia, Africa, and Latin America with a significant number of leprosy cases and 1 to 2 million people worldwide are visibly and irreversibly disabled due to past and present leprosy.

The nation’s first leprosarium, located in what is now known as Carville, Louisiana.

In 1921, the U.S. Public Health Service established the nation’s first leprosarium, located in what is now known as Carville, Louisiana. The leprosarium served as an institution for people with leprosy and a hospital for experiments with treatments for leprosy as well as a laboratory to study the organism. The center, which became known simply as “Carville,” became a refuge for leprosy patients and one of the premier centers of scientific research and testing in attempts to find a cure for the disease.

In 1941, the discovery of Promin, a sulfone drug, was shown to successfully cure leprosy, but this treatment also involved painful injections. Promin became known as the “Miracle of Carville.” In the 1950s, dapsone pills, pioneered by Dr. R.G. Cochrane at Carville, became the treatment of choice for leprosy. Dapsone worked wonderfully at first, but Mycobacterium leprae bacteria eventually began developing dapsone resistance.

In the 1970s, the first successful multidrug treatment (MDT) regimen for leprosy was developed through drug trials on the island of Malta. In 1981, The World Health Organization began recommending MDT, a combination of three drugs: dapsone, rifampicin, and clofazimine. The completion of MDT takes from 6 months to a year or even more, depending on clinical manifestations of the leprosy infection.

In 1986, the Carville facility became known Gillis W. Long Hansen’s Disease (Leprosy) Center, named after the distinguished U.S. Congressman, close friend, and associate of the people working and living with leprosy. During its century of service, Carville was home to several hundreds of patients, some of whom met and married there and spent a majority of their lives on the picturesque campus. When the hospital at Carville closed in 1998, its few remaining patients were reluctant to leave. The buildings and grounds were transferred to the State of Louisiana in 1998, and the clinical center relocated to Baton Rouge. A museum archiving the history of the Center and a National Cemetery remain open to the public. Some elderly patients continue to live at the facility.

Leprosy Today

At the beginning of 2010, the registered prevalence of leprosy in the world was 211,903 cases, and 244,796 new cases were detected during 2009, as reported by 141 countries (World Health Organization [WHO]).

Since the 1980s, when WHO initiated its Leprosy Elimination Project, more than 14 million cases have been cured. However, the number of new cases being detected annually is raising the unanswered questions about the infection source, transmission, and incubation period of leprosy. In other words, why are so many new cases detected in the midst of such a dramatic drop in the numbers of people living with the disease? This may be attributed to a number of factors including intensified efforts in case detection, and/or high transmission of the disease in certain areas.

Today, leprosy is found mainly in Angola, Brazil, Central African Republic, Democratic Republic of Congo, India, Madagascar, Mozambique, Nepal, and the United Republic of Tanzania. These countries account for 75 percent of the global leprosy burden, and they are taking steps to control the disease through information campaigns and by providing diagnostic and treatment services to all communities, including the poor and underserved, and by incorporating leprosy diagnosis and treatment into general health services.

Reference

NIAID has been supporting leprosy research around the world for many years. With the Mycobacterium leprae genome now identified, researchers are looking at several different approaches to combating leprosy.

Innovative research efforts are addressing such issues as transmission and the true extent of leprosy incidence. Studies are focusing on the areas of early detection (prior to developing clinical symptoms), prevention of nerve damage, surveillance of areas where drug resistance is occurring, and molecular epidemiology.

Tools for Researchers

Molecular tools have helped overcome challenges posed by the slow growth of M. leprae in vivo and its inability to grow in vitro. Other than humans, armadillos are the only animal known to be susceptible to leprosy. Because of this, colonies of armadillos have been important in research to model the disease. Since 1978, NIAID has supported contracts for the propagation of M. leprae in armadillos to derive sizable quantities of the bacterium, its DNA, and antigens as resources for researchers working throughout the world. The armadillo facility is located at the National Hansen’s Disease Program Laboratories (NHDP), Baton Rouge, Louisiana, and the M. leprae research reagents are being developed at Colorado State University, Fort Collins.

As part of these NIAID-funded contracts, investigators at NHDP are developing the armadillo as a research animal model for human leprosy and investigators at Colorado State University are developing improved skin test antigens to detect leprosy. Trials to determine the safety of new skin test antigens were conducted in volunteers in the United States and at the Anandaban Hospital in Nepal to determine the utility of a skin test for epidemiologic surveillance and diagnosis in leprosy-endemic regions.

Transmission Discovery

NIAID-funded scientists at NHDP are also using genomic knowledge of M. leprae to examine leprosy transmission. From earlier epidemiological studies, NIAID-funded scientists at NHDP knew that M. leprae had been found among wild armadillos in Texas and Louisiana, suggesting that human contact with infected armadillos might lead to infection. Recently, the research team, led by by Richard W. Truman, Ph.D., compared the gene sequences of M. leprae samples taken from humans and infected wild armadillos and found that 64% of human samples had a particular genotype that had never been seen before. What’s more, 85% of armadillo samples shared that same genotype.

These results showed that the two strains were related and that wild armadillos were a likely source of some human infections. But more importantly, it established leprosy as a zoonosis: an infectious disease that can be transmitted back and forth between animals and humans.

Next Steps

Priorities for research in leprosy today include genetic probes for molecular epidemiology, and new immunologic tests for early detection of leprosy before nerve damage occurs. The goals are to provide evidence on routes of transmission and incubation periods and to develop new tools to prevent and, ultimately, eradicate leprosy.